The effect of leucine infusion on substrate flux across the human forearm

In this study we examine the role of leucine infusion on amino acid and carbohydrate flux across the human forearm. Thirteen male volunteers of ideal body weight (103 ± 3%) were studied after an overnight fast. Five received an infusion of l-leucine (2.1 ± 0.07 μmol/kg/min) for 5 hr and 8 received physiologic saline as controls. Blood samples were obtained from arterialized hand vein and a deep forearm vein at 15-min intervals for 1 hr basal period and at 1-hr intervals for a 5-hr experimental period. Blood flow to the forearm was measured by capacitance plethysmography and balance ( Q ̇ ) across the forearm was calculated according to the Fick principle. Leucine infusion resulted in a reversal of Q ̇ leu ) from a net production of 17 ± 5 to a net uptake of 249 ± 23 nmol/100 g muscle/min ( P < 0.001) or 15% of the infused load. α-Keto-isocaproate release increased from 23 ± 4 to 48 ± 7 nmol/100 g muscle/min ( P < 0.05). Alanine output dropped by 57% (125 ± 22 to 53 ± 12 nmol/100 g muscle/min, P < 0.005), while glutamine output increased by 150% (131 ± 20 to 326 ± 31 nmol/100 g muscle/min, P < 0.005). Total alpha amino nitrogen (AAN output) by the forearm dropped by 60 and 48% within 1 and 2 hr of leucine infusion and returned thereafter to basal levels. The output of amino acids, other than the BCAA, progressively increased such that they were 75% of basal values by the end of leucine infusion (370 ± 75 vs 645 ± 115 nmol/100 g muscle/min, P < 0.005). Glucose uptake dropped and lactate release increased by 80% each. Insulin levels increased by 82%. These changes resulted in a 10% drop in glucose and a 25% increase in lactate levels. Ketone bodies and plasma FFA increased by 85 and 21%, respectively. We conclude that leucine infusion in overnight fasted man results in (a) a transient positive effect on nitrogen balance, followed by (b) an increase in glutamine output across the forearm to account for all the leucine retained, and (c) a minimal change in KIC output, thus suggesting that most of the leucine retained was completely oxidized across the forearm tissue. Furthermore leucine infusion exerted a glucose sparing effect by directly inhibiting glucose uptake across the forearm.